OCA at 15:15, 18 October 2023

OCA — Wed, 18 Oct 2023 15:15:46 GMT

←Older revision		Revision as of 15:15, 18 October 2023
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	==ACMSD in complex with diflunisal==		==ACMSD in complex with diflunisal==
-	<StructureSection load='7k12' size='340' side='right'caption='[[7k12]]' scene=''>	+	<StructureSection load='7k12' size='340' side='right'caption='[[7k12]], [[Resolution\|resolution]] 2.17Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K12 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7K12 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7k12]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7K12 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7k12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k12 OCA], [~~http~~://pdbe.org/7k12 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7k12 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7k12 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7k12 ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.17Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1FL:5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC+ACID'>1FL</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7k12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k12 OCA], [https://pdbe.org/7k12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7k12 RCSB], [https://www.ebi.ac.uk/pdbsum/7k12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7k12 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q83V25_PSEFL Q83V25_PSEFL]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of nicotinamide adenine dinucleotide (NAD(+)). In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (ACMSD) for further metabolism and energy production. Therefore, the inhibition of ACMSD increases NAD(+) levels. In this study, an Food and Drug Administration (FDA)-approved drug, diflunisal, was found to competitively inhibit ACMSD. The complex structure of ACMSD with diflunisal revealed a previously unknown ligand-binding mode and was consistent with the results of inhibition assays, as well as a structure-activity relationship (SAR) study. Moreover, two synthesized diflunisal derivatives showed half-maximal inhibitory concentration (IC50) values 1 order of magnitude better than diflunisal at 1.32 +/- 0.07 muM (22) and 3.10 +/- 0.11 muM (20), respectively. The results suggest that diflunisal derivatives have the potential to modulate NAD(+) levels. The ligand-binding mode revealed here provides a new direction for developing inhibitors of ACMSD.
		+
		+	Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway.,Yang Y, Borel T, de Azambuja F, Johnson D, Sorrentino JP, Udokwu C, Davis I, Liu A, Altman RA J Med Chem. 2020 Dec 28. doi: 10.1021/acs.jmedchem.0c01762. PMID:33369426<ref>PMID:33369426</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7k12" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Pseudomonas fluorescens]]
	[[Category: Liu A]]		[[Category: Liu A]]
	[[Category: Yang Y]]		[[Category: Yang Y]]

OCA at 05:56, 20 January 2021

OCA — Wed, 20 Jan 2021 05:56:17 GMT

←Older revision		Revision as of 05:56, 20 January 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7k12 ~~is ON HOLD~~	+	==ACMSD in complex with diflunisal==
-		+	<StructureSection load='7k12' size='340' side='right'caption='[[7k12]]' scene=''>
-	~~Authors~~: ~~Yang~~, Y., ~~Liu~~, A.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7K12 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7K12 FirstGlance]. <br>
-	~~Description: ACMSD in complex with diflunisal~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7k12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7k12 OCA], [http://pdbe.org/7k12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7k12 RCSB], [http://www.ebi.ac.uk/pdbsum/7k12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7k12 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Yang, Y~~]]	+	__TOC__
-	[[Category: ~~Liu, A~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Liu A]]
		+	[[Category: Yang Y]]

OCA: Protected "7k12" [edit=sysop:move=sysop]

OCA — Wed, 16 Sep 2020 07:05:14 GMT

Protected "7k12" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:05, 16 September 2020

OCA: New page: '''Unreleased structure''' The entry 7k12 is ON HOLD Authors: Yang, Y., Liu, A. Description: ACMSD in complex with diflunisal Category: Unreleased Structures Category: Yang, Y ...

OCA — Wed, 16 Sep 2020 07:05:12 GMT

New page: '''Unreleased structure''' The entry 7k12 is ON HOLD Authors: Yang, Y., Liu, A. Description: ACMSD in complex with diflunisal Category: Unreleased Structures Category: Yang, Y ...

New page

'''Unreleased structure'''

The entry 7k12 is ON HOLD

Authors: Yang, Y., Liu, A.

Description: ACMSD in complex with diflunisal
[[Category: Unreleased Structures]]
[[Category: Yang, Y]]
[[Category: Liu, A]]

7k12 - Revision history

OCA at 15:15, 18 October 2023

OCA at 05:56, 20 January 2021

OCA: Protected "7k12" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7k12 is ON HOLD Authors: Yang, Y., Liu, A. Description: ACMSD in complex with diflunisal Category: Unreleased Structures Category: Yang, Y ...